title: Sense transcription through the S region is essential for immunoglobulin class switch recombination.
abstract: Class switch recombination (CSR) occurs between highly repetitive sequences called switch (S) regions and is initiated by activation-induced cytidine deaminase (AID). CSR is preceded by a bidirectional transcription of S regions but the relative importance of sense and antisense transcription for CSR in vivo is unknown. We generated three mouse lines in which we attempted a premature termination of transcriptional elongation by inserting bidirectional transcription terminators upstream of Sμ, upstream of Sγ3 or downstream of Sγ3 sequences. The data show, at least for Sγ3, that sense transcriptional elongation across S region is absolutely required for CSR whereas its antisense counterpart is largely dispensable, strongly suggesting that sense transcription is sufficient for AID targeting to both DNA strands.
authors.affiliation: CNRS UMR 5089-IPBS (Institut de Pharmacologie et de Biologie Structurale) and Université Paul Sabatier III, Equipe 'Instabilité génétique et régulation transcriptionnelle', Toulouse Cedex, France.
authors.forename: Dania
authors.initials: D
authors.lastname: Haddad
authors.forename: Zéliha
authors.initials: Z
authors.lastname: Oruc
authors.forename: Nadine
authors.initials: N
authors.lastname: Puget
authors.forename: Nathalie
authors.initials: N
authors.lastname: Laviolette-Malirat
authors.forename: Magali
authors.initials: M
authors.lastname: Philippe
authors.forename: Claire
authors.initials: C
authors.lastname: Carrion
authors.forename: Marc
authors.initials: M
authors.lastname: Le Bert
authors.forename: Ahmed Amine
authors.initials: AA
authors.lastname: Khamlichi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics*; D016373:DNA, Antisense / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D007136:Immunoglobulins / Q000235:genetics; D051379:Mice; D026723:Polyadenylation; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D016373:DNA, Antisense; D007136:Immunoglobulins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase